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Unrooted phylogenetic tree (radial view) of homology Class I proteins consisting of Family Ia AroA and Family Iß AroA and KdsA subfamilies. The tree was generated with the neighbor-joining method. Yellow highlighting shows the "Class I" KDOP synthases on the lower left and the "Class I" DAHP synthases on the lower right (our AroA Iß ) that were asserted by Birck and Woodward (2001). The lineage leading to two higher plant KdsA sequences is highlighted in orange. A hypothetical root is indicated with a circle, and separate evolutionary events of loss of dependence upon metal for catalysis that are postulated are shown with arrows. Bootstrap values of 1000 per 1000 iterations supported the major nodes, and the order of branching within the various component clusters was generally supported with high bootstrap values. The manually adjusted multiple alignment used as input for the tree program contained complete sequences in order to better relate the results to those of Birck and Woodward (2001). The branching relationships within each major cluster are slightly different when extraneous N-terminal extensions were excised in order to analyze only the core catalytic region. The latter tree and input multiple alignment are available upon request.
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-manno-octulosonate8-phosphate (KDOP) synthases.DAHP is the initial product that is specifically com-mitted to the biosynthesis of aromatic amino acids and avariety of other aromatic compounds via the action ofDAHP synthase. KDOP is best known as a key precursorof lipopolysaccharide in gram-negative bacteria, but itswider distribution in capsular p...
Contexts in source publication
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... template for visualization of conserved motifs defined by invari- ant residues within the Family I 3-deoxy-ald-2- ulosonate-phosphate synthases. Invariant residues are displayed by color coding at the hierarchical levels of AroA I , AroA I , and KdsA. The distinctive Streptococ- cus sequences occupy an outlying position in the AroA I clade (see Fig. 2), and Fig. 1 shows in orange the posi- tions of 10 residues for which Streptococcus is the only exception to invariance in family AroA I . Vertical bars join invariant residues that are common to both AroA I and AroA I (5 residues), to both AroA I and KdsA (4 residues), or to the entire family (11 residues). Many other matches can be ...
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... Eco KdsA (representing 31 KdsA members) were extracted from a multiple alignment (available upon request). The gaps required in the overall alignment are shown as dashes. Eco AroA F , Eco KdsA, and Aae KdsA were studied by X-ray crystallography. The AroA proteins from Streptococcus are a distinctive divergent lineage within the I subfamily (see Fig. 2). Amino acid residues of Streptococcus AroA I proteins are highlighted in orange (second line) to show the 10 residues that are otherwise invariant in subfamily I, differing only in Streptococcus. Residue numbers are shown at the left and the right. Residues whose invariance is restricted to the AroA I , AroA I , or KdsA grouping are ...
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... displayed in gray. Vertical bars connect residues conserved between AroA I and AroA I (blue), between AroA I and KdsA (pink), or between the entire protein family (green). Metal-coordinating residues are labeled M ++ . the four established metal ligands are invariant. C-11 (Aae KdsA numbering) is conserved in the majority of KdsA sequences (see Fig. 2) but is substituted in the remainder (as illustrated by N-26 of Eco KdsA). The functional roles of some invariant residues for coordina- tion with substrates have been elucidated by the various studies of the crystal structures, and ongoing work should be additionally informative. Figure 2 shows results obtained from the neighbor- ...
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... functional roles of some invariant residues for coordina- tion with substrates have been elucidated by the various studies of the crystal structures, and ongoing work should be additionally informative. Figure 2 shows results obtained from the neighbor- joining program displayed as an unrooted tree. The AroA proteins split into two groups consistent with the Aroa I and AroA I divisions asserted by Subramaniam et al. (1998) and similar to the maximum likelihood tree pre- sented (their Fig. 3) by Birck and Woodard (2001), ex- cept for their unacceptable inclusion of two AroA II se- quences. ...
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... AroA proteins split into two groups consistent with the Aroa I and AroA I divisions asserted by Subramaniam et al. (1998) and similar to the maximum likelihood tree pre- sented (their Fig. 3) by Birck and Woodard (2001), ex- cept for their unacceptable inclusion of two AroA II se- quences. Figure 2 also shows the greater proximity of AroA I to KdsA than to AroA I . Although Birck and Woodard (2001) depict the KdsA proteins as a division of two distinct groups (their Fig. 2), there is in fact no divergence that is at all comparable to the divergence between AroA I and AroA I . ...
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... and similar to the maximum likelihood tree pre- sented (their Fig. 3) by Birck and Woodard (2001), ex- cept for their unacceptable inclusion of two AroA II se- quences. Figure 2 also shows the greater proximity of AroA I to KdsA than to AroA I . Although Birck and Woodard (2001) depict the KdsA proteins as a division of two distinct groups (their Fig. 2), there is in fact no divergence that is at all comparable to the divergence between AroA I and AroA I . Rather, their "Class I" group (shown in yellow) is a normal divergence that generally parallels expectations for 16S rRNA trees of the -division Proteobacteria themselves. The much heavier representation of sequences in the "Class ...
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... Fig. 2 the "Class I" DAHP synthases (AroA I ) and the "Class I" KdsA proteins, defined by Birck and Woodard (2001) as enzymes lacking any metal require- ment, are shown in yellow. Recently, an additional ex- ample of a nonmetallo KdsA protein has been described (Brabetz et al. 2000) that falls outside the "Class I" grouping (highlighted in ...
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... 2 the "Class I" DAHP synthases (AroA I ) and the "Class I" KdsA proteins, defined by Birck and Woodard (2001) as enzymes lacking any metal require- ment, are shown in yellow. Recently, an additional ex- ample of a nonmetallo KdsA protein has been described (Brabetz et al. 2000) that falls outside the "Class I" grouping (highlighted in orange in Fig. 2). Birck and Woodard (2001) dismiss the validity of obtaining any tree relationship of KDOP synthase and DAHP synthase on the grounds of "low sequence similarity." Yet the AroA I and AroA I groups are included together in one of their trees, despite the fact that these are more remote from one another than are AroA I and KdsA (Fig. 2). ...
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... in orange in Fig. 2). Birck and Woodard (2001) dismiss the validity of obtaining any tree relationship of KDOP synthase and DAHP synthase on the grounds of "low sequence similarity." Yet the AroA I and AroA I groups are included together in one of their trees, despite the fact that these are more remote from one another than are AroA I and KdsA (Fig. 2). They imply that "Class II" KDOP synthase and "Class II" DAHP synthases (defined as metalloenzymes) group together based upon the use of common metal- coordinating residues. Likewise, evolutionary linkage of "Class I" KDOP synthase and "Class I" DAHP synthase was asserted, based primarily on the alteration of a single ...
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... based upon the use of common metal- coordinating residues. Likewise, evolutionary linkage of "Class I" KDOP synthase and "Class I" DAHP synthase was asserted, based primarily on the alteration of a single metal-coordinating residue. They therefore assert an evo- lutionary relationship between the KdsA and the AroA I proteins shown in yellow in Fig. 2, on the one hand, and between AroA I and the remaining KdsA proteins, on the other hand. However, Fig. 2 shows that KdsA pro- teins, whether they be metalloenzymes or nonmetalloen- zymes, are more closely related to one another than to ...
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... KDOP synthase and "Class I" DAHP synthase was asserted, based primarily on the alteration of a single metal-coordinating residue. They therefore assert an evo- lutionary relationship between the KdsA and the AroA I proteins shown in yellow in Fig. 2, on the one hand, and between AroA I and the remaining KdsA proteins, on the other hand. However, Fig. 2 shows that KdsA pro- teins, whether they be metalloenzymes or nonmetalloen- zymes, are more closely related to one another than to ...
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... any AroA protein, whether metalloprotein (AroA I ) or putative nonmetalloprotein (AroA I ). At the higher hier- archical level KdsA and AroA I are more similar to one another than to AroA I , regardless of the presence or absence of a metal requirement. Although the tree shown in Fig. 2 is an unrooted tree, a reasonable speculation would be to place the root of the tree nearest the AroA I grouping since members of this group are the most widely distributed in nature (Gosset et al. 2001). A suggested evolutionary scenario (Fig. 2) that accommodates the metalloprotein character state with a correct tree relationship ...
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... to AroA I , regardless of the presence or absence of a metal requirement. Although the tree shown in Fig. 2 is an unrooted tree, a reasonable speculation would be to place the root of the tree nearest the AroA I grouping since members of this group are the most widely distributed in nature (Gosset et al. 2001). A suggested evolutionary scenario (Fig. 2) that accommodates the metalloprotein character state with a correct tree relationship requires at least three indepen- dent events where metal dependence for catalysis was lost. The assumption of the ancient existence of metal- coordinating residues as a primitive catalytic scaffold seems in line with current thinking. Three separate ...
Citations
... On the other hand, type Ib is present in Bacillus subtilis and Pyrococcus furiosus, is not a metalloenzyme, and can be classified as unregulated, phenylalanine-and tyrosine-regulated, and chorismate/prephenate-regulated enzymes based on the presence or absence of N-or C-terminal extensions (Light and Anderson 2013). Type II, which was first found in plants, has a size of 50 kDa and only shares a sequence homology of 10% with the Type I enzyme (Subramaniam et al. 1998;Jensen et al. 2002;Schofield et al. 2004;Zhao et al. 2019). It has isoforms that are regulated by Trp (Gosset et al. 2001), chorismate and Trp (Stuart and Hunter 1993;Walker et al. 1996) and are insensitive to chorismate and the three aromatic amino acids (Webby et al. 2005). ...
Absent in animals and with only seven enzymatic reactions toward the synthesis of chorismate and aromatic amino acids, the shikimate pathway is a crucial target for developing antimicrobial agents and herbicides. Although this pathway has been extensively studied in microorganisms related to human health, it reveals complexities in plants, as it takes part in primary and secondary metabolism. Obtaining enzyme inhibitors is essential to circumvent the occurrence of weeds resistant to commercially available herbicides and to help control human diseases, which has challenged researchers to search for new molecules and investigate their modes of action. By applying bioinformatics tools, thousands of enzyme inhibitors of this metabolic pathway can be prospected at a low cost and in a short time. Here, we revisit how the enzymes of the shikimate pathway have been characterized and update the status of their inhibitors in microorganisms and plants. This overview can be constructive in searching for enzyme inhibitors in the academic, human health, and agro-industrial fields.
... Type I DAHPS is comparatively more minor with less than 40 kDa of molecular weight, and primarily present in archaeal and prokaryotic organisms except for some eukaryotes like Saccharomyces cerevisiae (Hartmann et al., 2003). It is further classified into subtypes: type Ia and type Ib (Jensen et al., 2002). Type Ia are metalloenzymes while type Ib are non-metalloenzymes including some exceptions (Wu & Woodard, 2006). ...
The laxative properties of senna are attributed to the presence of sennosides produced in the plant. The low production level of sennosides in the plant is an important impediment to their growing demand and utilization. Understanding biosynthetic pathways helps to engineer them in terms of enhanced production. The biosynthetic pathways of sennoside production in plants are not completely known yet. However, attempts to get information on genes and proteins engaged in it have been made which decode involvement of various pathways including shikimate pathway. 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) is a key enzyme involved in sennosides production through the shikimate pathway. Unfortunately, there is no information available on proteomic characterization of DAHPS enzyme of senna (caDAHPS) resulting in lack of knowledge about its role. We for the first time characterized DAHPS enzyme of senna using in-silico analysis. To the best of our knowledge this is the first attempt to identify the coding sequence of caDAHPS by cloning and sequencing. We found Gln179, Arg175, Glu462, Glu302, Lys357 and His420 amino acids in the active site of caDAHPS through molecular docking. followed by molecular dynamic simulation. The amino acid residues, Lys182, Cys136, His460, Leu304, Gly333, Glu334, Pro183, Asp492 and Arg433 at the surface interact with PEP by van der Waals bonds imparting stability to the enzyme-substrate complex. Docking results were further validated by molecular dynamics. The presented in-silico analysis of caDAHPS will generate opportunities to engineer the sennoside biosynthesis in plants.Communicated by Ramaswamy H. Sarma.
... 17−19 DAHPS members belong to one of the two distinct family types, I and II, which have distinct molecular size and amino acid sequences. 20,21 More specifically, type I's are smaller than type II, with the former having masses of <40 kDa, whereas the latter have masses >50 kDa. Type 1 members, while sharing a common (β/α) 8 TIM barrel fold and an additional structural domain relevant for allosteric control, 10,22 can be further subdivided into type Iα and Iβ sequence subfamilies. ...
The shikimate pathway, which produces aromatic amino acids and key intermediates, is critical to the viability of the tuberculosis-causing pathogen Mycobacterium tuberculosis. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAHPS) catalyzes the first committed step of this pathway and possesses regulatory functions. Its active site contains two cysteinyls: one (Cys87) bound to a metal ion, while the other (Cys440) is in proximity to the first but is located on a connecting loop. This arrangement seemingly appeared as a disulfide linkage. However, Cys440 is not metal binding, and its positioning indicates that it could collapse the disulfide linkage. Hence, its potential role may be more than simply structural support of the active site fold. Using a multiscale computational approach, molecular dynamics (MD) simulations, and DFT-based calculations, the influence of Cys440 on the active site properties has been investigated. MD simulations reveal an unusually long disulfide bond, more than 3.0 Å, whereas DFT calculations identified two stable active site conformers in the triplet and quintet spin states. Analysis of group spin density distribution identified antiferromagnetic coupling in each conformer, which suggests their relatively low potential energy and stable conformations. The conformer in the triplet spin state could favor enzyme reactivity due to its low HOMO-LUMO energy gap. In addition, reduction of the Cys440 thiolate group results in collapse of the active site metal-ligand configuration with large exothermicity. Hence, Cys440 could activate and inactivate the enzyme. For the first time, the study revealed the role of Cys440 as being vital for the catalytic activity of the enzyme rather than solely for the structural stabilization of its active site. Thus, the findings may lead to a novel basis for antituberculosis drug design and development that would disrupt the contributions of the Cys440.
... Given that they differ in their physicochemical properties, amino acid sequences, quaternary structures, molecular mass, and occurrence in different bacteria, they were each analyzed differently. Both sequences of DAHPS isozymes were used in the MSA because they share a common 3D structure and were present in 14% of genomes analyzed [70][71][72][73][74][75]. In contrast, the two DHQase families were analyzed separately (DHQase I and II) because there is neither a unique amino acid sequence nor 3D similarity between the two [50,76]. ...
... The evolutionarily least conserved are DAHPS and DHQase I, which have 23% and 21% conserved residues, respectively. The lower conservation of DAHPS is not surprising because the sequences taken for MSA were distributed between both enzyme classes and have only 10% sequence identity [70][71][72]. On the other hand, CS is the most evolutionarily conserved of all enzymes in the shikimate pathway and contains 44% of residues with high conservation scores. ...
Enzymes belonging to the shikimate pathway have long been considered promising targets for antibacterial drugs because they have no counterpart in mammals and are essential for bacterial growth and virulence. However, despite decades of research, there are currently no clinically relevant antibacterial drugs targeting any of these enzymes, and there are legitimate concerns about whether they are sufficiently druggable, i.e., whether they can be adequately modulated by small and potent drug-like molecules. In the present work, in silico analyses combining evolutionary conservation and druggability are performed to determine whether these enzymes are candidates for broad-spectrum antibacterial therapy. The results presented here indicate that the substrate-binding sites of most enzymes in this pathway are suitable drug targets because of their reasonable conservation and druggability scores. An exception was the substrate-binding site of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase, which was found to be undruggable because of its high content of charged residues and extremely high overall polarity. Although the presented study was designed from the perspective of broad-spectrum antibacterial drug development, this workflow can be readily applied to any antimicrobial target analysis, whether narrow- or broad-spectrum. Moreover, this research also contributes to a deeper understanding of these enzymes and provides valuable insights into their properties.
... WP_003812536.1 protein is encode by dapD gene and is involved in the process of L-lysine biosynthesis inside aminoacid biosynthesis (UniProt, 2019). The protein WP_003813703.1 is encode by kdsA gene, which has important functions in the carbohydrate synthesis pathway and the lipopolysaccharide synthesis pathway, resulting in the formation of keto-3-deoxy-D-manno-octulosonic acid, which is a key sugar-acid in the biogenesis of the bacterial outer membrane (Jensen et al., 2002;Strohmaier et al., 1995;UniProt, 2019). All these proteins perform roles in vital bacterial processes, and then changes in these processes can compromise bacterial integrity. ...
Pertussis is a highly contagious respiratory disease caused by Bordetella pertussis, a Gram-negative bacterium described over a century ago. Despite broad vaccine coverage and treatment options, the disease is remerging as a public health problem especially in infants and older children. Recent data indicate re-emergence of the disease is related to bacterial resistance to immune defences and decreased vaccine effectiveness, which obviously suggests the need of new effective vaccines and drugs. In an attempt to contribute with solutions to this great challenge, bioinformatics tools were used to genetically comprehend the species of these bacteria and predict new vaccines and drug targets. In fact, approaches were used to analysis genomic plasticity, gene synteny and species similarities between the 20 genomes of Bordetella pertussis already available. Furthermore, it was conducted reverse vaccinology and docking analysis to identify proteins with potential to become vaccine and drug targets, respectively. The analyses showed the 20 genomes belongs to a homogeneous group that has preserved most of the genes over time. Besides that, were found genomics islands and good proteins to be candidates for vaccine and drugs. Taken together, these results suggests new possibilities that may be useful to develop new vaccines and drugs that will help the prevention and treatment strategies of pertussis disease caused by these Bordetella strains.
Communicated by Ramaswamy H. Sarma
... Type II enzymes are larger, with molecular masses over 50 kDa. Although there is less than 10% sequence identity between types I and II, all DAHPS enzymes share a common (βα) TIM barrel catalytic domain, with extra-barrel elements related to allosteric function [26][27][28]. DAHPS activity is allosterically regulated by all three aromatic amino acids produced by the pathway-phenylalanine (Phe), tyrosine (Tyr) and tryptophan (Trp)-therefore being the major flow control point for the shikimate pathway [17,26]. ...
Roughly a third of the world’s population is estimated to have latent Mycobacterium tuberculosis infection, being at risk of developing active tuberculosis (TB) during their lifetime. Given the inefficacy of prophylactic measures and the increase of drug-resistant M. tuberculosis strains, there is a clear and urgent need for the development of new and more efficient chemotherapeutic agents, with selective toxicity, to be implemented on patient treatment. The component enzymes of the shikimate pathway, which is essential in mycobacteria and absent in humans, stand as attractive and potential targets for the development of new drugs to treat TB. This review gives an update on published work on the enzymes of the shikimate pathway and some insight on what can be potentially explored towards selective drug development.
... DAHPS enzymes have been divided into two classes (types I and II) based on the phylogenetic analysis ( Fig. 1B) (Walker et al., 1996). Type I enzymes are less than 40 kDa in size and are parsed into two subclasses (Iα and Iβ) (Jensen et al., 2002;Subramaniam et al., 1998), while type II enzymes are defined as "plant-like" homologs and are larger than type I enzymes (> 50 kDa per subunit) (Subramaniam et al., et al., 2013;Hartmann et al., 2003;Shumilin et al., 1999). In Escherichia coli, there are three DAHPS isozymes, which are feedback regulated by different aromatic amino acids (Shumilin et al., 1999). ...
3-Deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHPS) is responsible for the biosynthesis of essential aromatic compounds in microorganisms and plants. It plays a crucial role in the regulation of the carbon flow into the shikimate pathway. Until now, the crystal structures and regulatory mechanisms of dimeric DAHPS enzymes from type Iα subclass have not been reported. Here, we reported dimeric structures of the tyrosine-regulated DAHPS from Escherichia coli, both in its apo form and complex with the inhibitor tyrosine at 2.5 and 2.0 Å resolutions, respectively. DAHPS(Tyr) has a typical (β/α) 8 TIM barrel, which is decorated with an N-terminal extension and an antiparallel β sheet, β6a/β6b. Inhibitor tyrosine binds at a cavity formed by residues of helices α3, α4, strands β6a, β6b and the adjacent loops, and directly interacts with residues P148, Q152, S181, I213 and N8 * . Although the small angle X-ray scattering profiles from DAHPS(Tyr) with and without tyrosine shows that tyrosine binding leaves most of DAHPS(Tyr) structures unaffected. The comparison of the liganded and unliganded crystal structures reveals that conformational changes of residues P148, Q152 and I213 initiate a transmission pathway to propagate the allosteric signal from the tyrosine-binding site to the active site, which is different from DAHPS(Phe), a phenylalanine-regulated isozyme from E. coli. In addition, mutations of five tyrosine-binding residues P148, Q152, S181, I213 and N8 * leads to tyrosine-resistant DAHPS(Tyr) enzymes. These findings provide a new insight into the regulatory mechanism of DAHPS enzymes and a basis for further engineering studies.
... DAHPSs can be classified as type I or type II according to their molecular dimension: type I is < 40 kDa, and type II is 50 kDa (Gosset et al. 2001;Jensen et al. 2002). Type I DAHPS is divided into types I α and I β (Jensen et al. 2002). ...
... DAHPSs can be classified as type I or type II according to their molecular dimension: type I is < 40 kDa, and type II is 50 kDa (Gosset et al. 2001;Jensen et al. 2002). Type I DAHPS is divided into types I α and I β (Jensen et al. 2002). The DAHPSs from Escherichia coli, Saccharomyces cerevisiae, and N. meningitidis represent type I α . ...
3-Deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAHPS) is a key rate-limiting enzyme in aromatic amino acid anabolism. A new Iβ-type DAHPS gene (aro1A) was identified in a metagenomic library from subtropical marine mangrove sediment. The gene encoded a polypeptide composed of 272 amino acids and had a maximum similarity of 52.4% to a known DAHPS at the amino acid level. Multiple sequence alignment, homologous modeling, and molecular docking showed that Aro1A had the typical (β/α)8 barrel-shaped catalytic structural domain of DAHPS. The motifs and amino acid residues involved in the combination of substrates and metal ligand were highly conservative with the known DAHPS. The putative DAHPS gene was subcloned into a pET-30a(+) vector and was overexpressed in Escherichia coli Rosetta (DE3) cells. The recombinant protein was purified to homogeneity. The maximum activity for the recombinant Aro1A protein occurred at pH 8.0 and 40 °C. Ba²⁺ and Ca²⁺ stimulated the activity of Aro1A protein. The enzyme showed high affinity and catalytic efficiency (KmPEP = 19.58 μM, VmaxPEP = 29.02 μM min⁻¹, and kcatPEP/KmPEP = 0.88 s⁻¹ μM⁻¹) under optimal reaction conditions. The enzymatic property of Aro1A indicates its potential in aromatic amino acid industrial production.
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The online version of this article (10.1186/s13568-019-0742-4) contains supplementary material, which is available to authorized users.
... Throughout the last decade we have given considerable thought to issues of nomenclature in relationship to what is a relatively large and complex metabolic system. We have implemented a continuum of suggestions [5][6][7][8][9][10][11][12], some of which have been further revised or even abandoned in favor of perceived improvements that are presented here. This has at least been a starting point of experience for an issue that is not trivial. ...
... In other words, the phylogenetic thread can usually be traced with respect to functional roles, even though the thread may have a meandering character. New sequence queries that are addressed to a correct background of annotation will generate the correct functional annotation [9]. ...
Background: The accurate annotation of functional roles for newly sequenced genes of genomes is not a simple matter. Function is, of course, related to amino-acid sequence and to domain structure but not always in straightforward ways. Even where given functional roles have been identified experimentally, the application of an uneven and erratic nomenclature has generated confusion on the part of annotators and has produced errors that tend to become progressively compounded in database repositories. Results: The pathway that is deployed in nature for aromatic biosynthesis exemplifies an accumulation of chaotic nomenclature and a variety of annotation dilemmas. We view this pathway as one that is sufficiently complex to pose most of the common problems, and yet is one that at the same time is of a manageable size. A set of guidelines has been developed for naming genes of aromatic-pathway biosynthesis and the corresponding gene products, and we suggest that these can be generalized for application to other metabolic pathways. Conclusion: A system of nomenclature for aromatic biosynthesis is presented that is logical, consistent, and evolutionarily informative.
... Throughout the last decade we have given considerable thought to issues of nomenclature in relationship to what is a relatively large and complex metabolic system. We have implemented a continuum of suggestions [5][6][7][8][9][10][11][12], some of which have been further revised or even abandoned in favor of perceived improvements that are presented here. This has at least been a starting point of experience for an issue that is not trivial. ...
... In other words, the phylogenetic thread can usually be traced with respect to functional roles, even though the thread may have a meandering character. New sequence queries that are addressed to a correct background of annotation will generate the correct functional annotation [9]. ...
Background: The accurate annotation of functional roles for newly sequenced genes of genomes is not a simple matter. Function is, of course, related to amino-acid sequence and to domain structure but not always in straightforward ways. Even where given functional roles have been identified experimentally, the application of an uneven and erratic nomenclature has generated confusion on the part of annotators and has produced errors that tend to become progressively compounded in database repositories. Results: The pathway that is deployed in nature for aromatic biosynthesis exemplifies an accumulation of chaotic nomenclature and a variety of annotation dilemmas. We view this pathway as one that is sufficiently complex to pose most of the common problems, and yet is one that at the same time is of a manageable size. A set of guidelines has been developed for naming genes of aromatic-pathway biosynthesis and the corresponding gene products, and we suggest that these can be generalized for application to other metabolic pathways. Conclusion: A system of nomenclature for aromatic biosynthesis is presented that is logical, consistent, and evolutionarily informative.
